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The Cerebellum

, Volume 13, Issue 1, pp 17–28 | Cite as

Spinocerebellar Ataxias in Brazil—Frequencies and Modulating Effects of Related Genes

  • Raphael Machado de Castilhos
  • Gabriel Vasata Furtado
  • Tailise Conte Gheno
  • Paola Schaeffer
  • Aline Russo
  • Orlando Barsottini
  • José Luiz Pedroso
  • Diego Z. Salarini
  • Fernando Regla Vargas
  • Maria Angélica de Faria Domingues de Lima
  • Clécio Godeiro
  • Luiz Carlos Santana-da-Silva
  • Maria Betânia Pereira Toralles
  • Silvana Santos
  • Hélio van der LindenJr
  • Hector Yuri Wanderley
  • Paula Frassineti Vanconcelos de Medeiros
  • Eliana Ternes Pereira
  • Erlane Ribeiro
  • Maria Luiza Saraiva-Pereira
  • Laura Bannach JardimEmail author
  • on behalf of Rede Neurogenetica
Original Paper

Abstract

This study describes the frequency of spinocerebellar ataxias and of CAG repeats range in different geographical regions of Brazil, and explores the hypothetical role of normal CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes on age at onset and on neurological findings. Patients with symptoms and family history compatible with a SCA were recruited in 11 cities of the country; clinical data and DNA samples were collected. Capillary electrophoresis was performed to detect CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17, and DRPLA associated genes, and a repeat primed PCR was used to detect ATTCT expansions at SCA10 gene. Five hundred forty-four patients (359 families) were included. There were 214 SCA3/MJD families (59.6 %), 28 SCA2 (7.8 %), 20 SCA7 (5.6 %), 15 SCA1 (4.2 %), 12 SCA10 (3.3 %), 5 SCA6 (1.4 %), and 65 families without a molecular diagnosis (18.1 %). Divergent rates of SCA3/MJD, SCA2, and SCA7 were seen in regions with different ethnic backgrounds. 64.7 % of our SCA10 patients presented seizures. Among SCA2 patients, longer ATXN3 CAG alleles were associated with earlier ages at onset (p < 0.036, linear regression). A portrait of SCAs in Brazil was obtained, where variation in frequencies seemed to parallel ethnic differences. New potential interactions between some SCA-related genes were presented.

Keywords

Spinocerebellar ataxias SCA3/MJD SCA2 SCA7 SCA10 Modifier genes 

Notes

Acknowledgments

We would like to thank the patients and their families for taking part in this study. We would also like to thank Thais Santa Rita for her technical assistance; Vanessa Erichsen Emmel and Alexis Trott for their contribution in early stages of this project; and Pedro Braga-Neto, Isabel Cristina Neves de Souza, and Raimunda Helena Feio for their contribution in recruiting some patients. This study was supported by FAPERGS, CNPq, CAPES, INAGEMP, and FIPE-HCPA. Castilhos RM was supported by INAGEMP. Furtado GV was supported by CAPES. Gheno TC, Russo A, Saraiva-Pereira ML, and Jardim LB were supported by CNPq.

Conflict of Interest

The authors state that there is no potential conflict of interest

Supplementary material

12311_2013_510_Fig3_ESM.jpg (19 kb)
ESM Fig. 1

Correlations between the expanded CAG repeats and ages at onset in SCA1, SCA2, SCA3/MJD, SCA6, and SCA7 patients of the present series (JPEG 18 kb)

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High resolution image (TIFF 1249 kb)
12311_2013_510_Fig4_ESM.jpg (19 kb)
ESM Fig. 2

Distribution of the normal large CAG repeats at ATXN2 and at CACNA1A genes, in 102 SCA3/MJD patients studied by the three-panels approach (first and second rows), according to the presence or absence of abnormalities of ocular movement, nystagmus, dystonic movements, palpebral retraction, and absent reflexes. Distribution of the expanded repeats at ATXN3 gene in 230 SCA3/MJD patients (third row), according to the presence or absence of abnormalities of ocular movement, dystonic movements, and absent reflexes (JPEG 19 kb)

12311_2013_510_MOESM2_ESM.tif (7.1 mb)
High resolution image (TIFF 7301 kb)
12311_2013_510_Fig5_ESM.jpg (13 kb)
ESM Fig. 3

Distribution of the large CAG repeat at ATXN1 according to the presence of ophthalmoparesis in 49 SCA2 patients (JPEG 13 kb)

12311_2013_510_MOESM3_ESM.tif (4 mb)
High resolution image (TIFF 4115 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Raphael Machado de Castilhos
    • 1
    • 21
    • 22
  • Gabriel Vasata Furtado
    • 2
    • 21
  • Tailise Conte Gheno
    • 2
    • 21
  • Paola Schaeffer
    • 1
  • Aline Russo
    • 1
  • Orlando Barsottini
    • 3
  • José Luiz Pedroso
    • 3
  • Diego Z. Salarini
    • 4
  • Fernando Regla Vargas
    • 5
    • 6
    • 7
  • Maria Angélica de Faria Domingues de Lima
    • 6
    • 7
  • Clécio Godeiro
    • 8
  • Luiz Carlos Santana-da-Silva
    • 9
    • 22
  • Maria Betânia Pereira Toralles
    • 10
  • Silvana Santos
    • 11
    • 22
  • Hélio van der LindenJr
    • 12
  • Hector Yuri Wanderley
    • 13
  • Paula Frassineti Vanconcelos de Medeiros
    • 14
  • Eliana Ternes Pereira
    • 15
  • Erlane Ribeiro
    • 16
  • Maria Luiza Saraiva-Pereira
    • 17
    • 18
    • 21
    • 22
  • Laura Bannach Jardim
    • 17
    • 19
    • 20
    • 21
    • 22
    Email author
  • on behalf of Rede Neurogenetica
  1. 1.Medical Genetics ServiceHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  2. 2.Laboratory of Genetic IdentificationHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Setor de Neurologia Geral e Ataxias. Disciplina de Neurologia Clínica da UNIFESP-Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Ambulatório de Distúrbios do Movimento e NeurogenéticaDisciplina de Neurologia da Santa Casa de São PauloSão PauloBrazil
  5. 5.Universidade Federal do Estado do Rio de JaneiroRio de JaneiroBrazil
  6. 6.Post-Graduation ProgramUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  7. 7.Genetic Counseling ProgramInstituto Nacional do CâncerRio de JaneiroBrazil
  8. 8.Universidade Federal do Rio Grande do NorteNatalBrazil
  9. 9.Laboratório de Erros Inatos do Metabolismo, Instituto de Ciências BiológicasUniversidade Federal do ParáBelém do ParáBrazil
  10. 10.Universidade Federal da BahiaSalvadorBrazil
  11. 11.Universidade Estadual da ParaíbaCampina GrandeBrazil
  12. 12.Centro de Reabilitação Dr. Henrique SantilloGoiâniaBrazil
  13. 13.APAE de VitóriaEspírito SantoBrazil
  14. 14.Universidade Federal de Campina GrandeParaíbaBrazil
  15. 15.Universidade Federal de Santa CatarinaFlorianópolisBrazil
  16. 16.Associação Cearense de Doenças GenéticasFortalezaBrazil
  17. 17.Medical Genetics Service and Laboratory of Genetic IdentificationHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  18. 18.Department of BiochemistryUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  19. 19.Department of Internal MedicineUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  20. 20.Post-Graduation Program in Medical SciencesUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  21. 21.Post-Graduation Program in Genetics and Molecular BiologyUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  22. 22.Instituto Nacional de Genética Médica Populacional (INAGEMP)Porto AlegreBrazil

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